There are three objectives in the present proposal: (1) to determine the structure of the crotoxin complex from Crotalus d. terrificus by low dose electron diffraction methods, (2) to determine the molecular interaction between the crotoxin and the purified acetylcholine receptor membrane from T. Californica by binding kinetic analysis together with electron microscopy, and (3) to search for experimental conditions in reconstituting the receptor proteins that would form a highly ordered two dimensional array and would also maintain its specific activity in binding with the neurotoxin. The three dimensional structure of the crotoxin complex will be reconstructed to 5 angstrom units resolution by computer processing techniques from the low dose electron diffraction and image intensities collected at different tilting angles in a 100 keV transmission electron microscope. The glucose embeddment technique will be used to maintain the hydration of the crotoxin complex thin crystal inside the microscope vaccum. Nuclear track emulsion (NTB3), which has been found to be a more effective recording medium for low dose microscopy, will be used for the data recording. Acetylcholine receptor membrane will be isolated from the T. Californica according to the published procedures. Kinetic studies will be conducted to demonstrate the presence of specific interaction between the crotoxin and the purified receptor membrane, and to determine the dissociation constant and the possible binding domain in the acetylcholine receptor membrane. Frozen hydrated, unstained specimen preparation methods will be utilized in obtaining electron images of the acetylcholine receptor membrane and of the crotoxin-acetylcholine receptor membrane complex in order to visualize the quarternary structure of the receptor proteins and the molecular arrangement of the toxin-receptor complex. If the purified receptor membrane is found non-periodic, we will attempt to reconstitute the receptor membrane protein in a highly crystalline array by using different lipid compositions and temperatures. The objective of the last part of the proposal is to prepare the membrane in a crystalline form so that the structure of the membrane receptor-neurotoxin complex can be studied at high resolution.